Transcription factor RBP-J-mediated signaling represses the differentiation of neural stem cells into intermediate neural progenitors

2009 ◽  
Vol 40 (4) ◽  
pp. 442-450 ◽  
Author(s):  
Fang Gao ◽  
Qi Zhang ◽  
Min-Hua Zheng ◽  
Hui-Ling Liu ◽  
Yi-Yang Hu ◽  
...  
Keyword(s):  
Stem Cells ◽  
Transcription Factor ◽  
Neural Stem Cells ◽  
Neural Progenitors

scholarly journals Homeodomain protein Six4 prevents the generation of supernumerary Drosophila type II neuroblasts and premature differentiation of intermediate neural progenitors

PLoS Genetics ◽  
2021 ◽  
Vol 17 (2) ◽  
pp. e1009371
Author(s):  
Rui Chen ◽  
Yanjun Hou ◽  
Marisa Connell ◽  
Sijun Zhu
Keyword(s):  
Stem Cells ◽  
Transcription Factor ◽  
Neural Stem Cells ◽  
Neurological Diseases ◽  
Neural Progenitors ◽  
Homeodomain Protein ◽  
Type Ii ◽  
Trimeric Complex ◽  
Expression And Activity

In order to boost the number and diversity of neurons generated from neural stem cells, intermediate neural progenitors (INPs) need to maintain their homeostasis by avoiding both dedifferentiation and premature differentiation. Elucidating how INPs maintain homeostasis is critical for understanding the generation of brain complexity and various neurological diseases resulting from defects in INP development. Here we report that Six4 expressed in Drosophila type II neuroblast (NB) lineages prevents the generation of supernumerary type II NBs and premature differentiation of INPs. We show that loss of Six4 leads to supernumerary type II NBs likely due to dedifferentiation of immature INPs (imINPs). We provide data to further demonstrate that Six4 inhibits the expression and activity of PntP1 in imINPs in part by forming a trimeric complex with Earmuff and PntP1. Furthermore, knockdown of Six4 exacerbates the loss of INPs resulting from the loss of PntP1 by enhancing ectopic Prospero expression in imINPs, suggesting that Six4 is also required for preventing premature differentiation of INPs. Taken together, our work identified a novel transcription factor that likely plays important roles in maintaining INP homeostasis.

scholarly journals Dissecting Hes-centered transcriptional networks in neural stem cell maintenance and tumorigenesis in Drosophila

2020 ◽  
Author(s):  
Srivathsa S. Magadi ◽  
Chrysanthi Voutyraki ◽  
Gerasimos Anagnostopoulos ◽  
Evanthia Zacharioudaki ◽  
Ioanna K. Poutakidou ◽  
...  
Keyword(s):  
Stem Cells ◽  
Nervous System ◽  
Transcription Factor ◽  
Stem Cell ◽  
Neural Stem Cells ◽  
Cell Fate ◽  
Asymmetric Cell Division ◽  
Transcriptional Networks ◽  
Malignant Tumours ◽  
Stem Cell Maintenance

ABSTRACTNeural stem cells divide during embryogenesis and post embryonic development to generate the entire complement of neurons and glia in the nervous system of vertebrates and invertebrates. Studies of the mechanisms controlling the fine balance between neural stem cells and more differentiated progenitors have shown that in every asymmetric cell division progenitors send a Delta-Notch signal back to their sibling stem cells. Here we show that excessive activation of Notch or overexpression of its direct targets of the Hes family causes stem-cell hyperplasias in the Drosophila larval central nervous system, which can progress to malignant tumours after allografting to adult hosts. We combined transcriptomic data from these hyperplasias with chromatin occupancy data for Dpn, a Hes transcription factor, to identify genes regulated by Hes factors in this process. We show that the Notch/Hes axis represses a cohort of transcription factor genes. These are excluded from the stem cells and promote early differentiation steps, most likely by preventing the reversion of immature progenitors to a stem-cell fate. Our results suggest that Notch signalling sets up a network of mutually repressing stemness and anti-stemness transcription factors, which include Hes proteins and Zfh1, respectively. This mutual repression ensures robust transition to neuronal and glial differentiation and its perturbation can lead to malignant transformation.

scholarly journals Demyelination Regulates the Circadian Transcription Factor BMAL1 to Signal Adult Neural Stem Cells to Initiate Oligodendrogenesis

Cell Reports ◽  
2020 ◽  
Vol 33 (7) ◽  
pp. 108394
Author(s):  
Suihong Huang ◽  
Ming Ho Choi ◽  
Hao Huang ◽  
Xin Wang ◽  
Yu Chen Chang ◽  
...  
Keyword(s):  
Stem Cells ◽  
Transcription Factor ◽  
Neural Stem Cells ◽  
Adult Neural Stem Cells ◽  
Circadian Transcription

Overexpression of midbrain-specific transcription factor Nurr1 modifies susceptibility of mouse neural stem cells to neurotoxins

2002 ◽  
Vol 333 (1) ◽  
pp. 74-78 ◽  
Author(s):  
Myung Ae Lee ◽  
Hye-Souk Lee ◽  
Hyun Soo Lee ◽  
Kyung G. Cho ◽  
Byung Kwan Jin ◽  
...  
Keyword(s):  
Stem Cells ◽  
Transcription Factor ◽  
Neural Stem Cells ◽  
Specific Transcription Factor

scholarly journals The transcription factor Nerfin-1 prevents reversion of neurons into neural stem cells

2015 ◽  
Vol 29 (2) ◽  
pp. 129-143 ◽  
Author(s):  
Francesca Froldi ◽  
Milan Szuperak ◽  
Chen-Fang Weng ◽  
Wei Shi ◽  
Anthony T. Papenfuss ◽  
...  
Keyword(s):  
Stem Cells ◽  
Transcription Factor ◽  
Neural Stem Cells

scholarly journals Selective influence of Sox2 on POU transcription factor binding in embryonic and neural stem cells

EMBO Reports ◽  
2015 ◽  
Vol 16 (9) ◽  
pp. 1177-1191 ◽  
Author(s):  
Tapan Kumar Mistri ◽  
Arun George Devasia ◽  
Lee Thean Chu ◽  
Wei Ping Ng ◽  
Florian Halbritter ◽  
...  
Keyword(s):  
Stem Cells ◽  
Transcription Factor ◽  
Neural Stem Cells ◽  
Transcription Factor Binding ◽  
Factor Binding ◽  
Selective Influence

scholarly journals p53 controls genomic stability and temporal differentiation of human neural stem cells and affects neural organization in human brain organoids

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Ana Marin Navarro ◽  
Robin Johan Pronk ◽  
Astrid Tjitske van der Geest ◽  
Ganna Oliynyk ◽  
Ann Nordgren ◽  
...  
Keyword(s):  
Stem Cells ◽  
Neural Stem Cells ◽  
Human Brain ◽  
Genomic Stability ◽  
Neural Progenitors ◽  
Ips Cell ◽  
Human Neural Stem Cells ◽  
Neural Organization ◽  
Mature Neurons ◽  
Induced Pluripotent

AbstractIn this study, we take advantage of human induced pluripotent stem (iPS) cell-derived neural stem cells and brain organoids to study the role of p53 during human brain development. We knocked down (KD) p53 in human neuroepithelial stem (NES) cells derived from iPS cells. Upon p53KD, NES cells rapidly show centrosome amplification and genomic instability. Furthermore, a reduced proliferation rate, downregulation of genes involved in oxidative phosphorylation (OXPHOS), and an upregulation of glycolytic capacity was apparent upon loss of p53. In addition, p53KD neural stem cells display an increased pace of differentiating into neurons and exhibit a phenotype corresponding to more mature neurons compared to control neurons. Using brain organoids, we modeled more specifically cortical neurogenesis. Here we found that p53 loss resulted in brain organoids with disorganized stem cell layer and reduced cortical progenitor cells and neurons. Similar to NES cells, neural progenitors isolated from brain organoids also show a downregulation in several OXPHOS genes. Taken together, this demonstrates an important role for p53 in controlling genomic stability of neural stem cells and regulation of neuronal differentiation, as well as maintaining structural organization and proper metabolic gene profile of neural progenitors in human brain organoids.

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